Miracle-dz/UniFAR-FTUs huggingface dataset:
Post-ER Stress Biogenesis of Golgi Is Governed by Giantin

Background: The Golgi apparatus undergoes disorganization in response to stress, but it is able to restore compact and perinuclear structure under recovery. This self-organization mechanism is significant for cellular homeostasis, but remains mostly elusive, as does the role of giantin, the largest Golgi matrix dimeric protein. Methods: In HeLa and different prostate cancer cells, we used the model of cellular stress induced by Brefeldin A (BFA). The conformational structure of giantin was assessed by proximity ligation assay and atomic force microscopy. The post-BFA distribution of Golgi resident enzymes was examined by 3D SIM high-resolution microscopy. Results: We detected that giantin is rather flexible than an extended coiled-coil dimer and BFA-induced Golgi disassembly was associated with giantin monomerization. A fusion of the nascent Golgi membranes after BFA washout is forced by giantin re-dimerization via disulfide bond in its luminal domain and assisted by Rab6a GTPase. GM130-GRASP65-dependent enzymes are able to reach the nascent Golgi membranes, while giantin-sensitive enzymes appeared at the Golgi after its complete recovery via direct interaction of their cytoplasmic tail with N-terminus of giantin. Conclusion: Post-stress recovery of Golgi is conducted by giantin dimer and Golgi proteins refill membranes according to their docking affiliation rather than their intra-Golgi location.
Big Data – How to Realize the Promise

The increasing volume and complexity of data now being captured across multiple settings and devices offers the opportunity to deliver a better characterization of diseases, treatments, and the performance of medicinal products in individual healthcare systems. Such data sources, commonly labeled as big data, are generally large, accumulating rapidly, and incorporate multiple data types and forms. Determining the acceptability of these data to support regulatory decisions demands an understanding of data provenance and quality in addition to confirming the validity of new approaches and methods for processing and analyzing these data. The Heads of Agencies and the European Medicines Agency Joint Big Data Taskforce was established to consider these issues from the regulatory perspective. This review reflects the thinking from its first phase and describes the big data landscape from a regulatory perspective and the challenges to be addressed in order that regulators can know when and how to have confidence in the evidence generated from big datasets.
The salivary gland proteome of root-galling grape phylloxera (Daktulosphaira vitifoliae Fitch) feeding on Vitis spp.

The successful parasitisation of a plant by a phytophagous insect is dependent on the delivery of effector molecules into the host. Sedentary gall forming insects, such as grape phylloxera (Daktulosphaira vitifoliae Fitch, Phylloxeridae), secrete multiple effectors into host plant tissues that alter or modulate the cellular and molecular environment to the benefit of the insect. The identification and characterisation of effector proteins will provide insight into the host-phylloxera interaction specifically the gall-induction processes and potential mechanisms of plant resistance. Using proteomic mass spectrometry and in-silico secretory prediction, 420 putative effectors were determined from the salivary glands or the root-feeding D. vitifoliae larvae reared on Teleki 5C (V. berlandieri x V. riparia). Among them, 170 conserved effectors were shared between D. vitifoliae and fourteen phytophagous insect species. Quantitative RT-PCR analysis of five conserved effector candidates (protein disulfide-isomerase, peroxidoredoxin, peroxidase and a carboxypeptidase) revealed that their gene expression decreased, when larvae were starved for 24 h, supporting their assignment as effector molecules. The D. vitifoliae effectors identified here represent a functionally diverse group, comprising both conserved and unique proteins that provide new insight into the D. vitifoliae–Vitis spp. interaction and the potential mechanisms by which D. vitifoliae establishes the feeding site, suppresses plant defences and modulates nutrient uptake.
Expression of a Chromoplast-Specific Lycopene β-Cyclase Gene (CYC-B) Is Implicated in Carotenoid Accumulation and Coloration in the Loquat

Carotenoids are the principal pigments in the loquat. Although the metabolic pathway of plant carotenoids has been extensively investigated, few studies have been explored the regulatory mechanisms of loquat carotenoids because knowledge of the loquat genome is incomplete. The chromoplast-specific lycopene β-cyclase gene (CYC-B) could catalyze cyclization of lycopene to β-carotene. In this study, the differential accumulation patterns of loquat with different colors were analyzed and virus-induced gene silencing (VIGS) was utilized in order to verify CYC-B gene function. Using a cloning strategy of homologous genes, a CYC-B gene orthologue was successfully identified from the loquat. At a later stage of maturation, CYC-B gene expression and carotenoids concentrations in the ‘Dawuxing’ variety were higher than in ‘Chuannong 1-5-9′, possibly leading to the difference in pulp coloration of loquat. Interference of CYC-B gene expression in the loquat demonstrated clear visual changes. The green color in negative control fruits became yellow, while TRV2-CYC-B silenced fruits remained green. CYC-B gene expression and total carotenoid content in the pulp decreased by 32.5% and 44.1%, respectively. Furthermore, multiple key genes in the carotenoid metabolic pathway synergistically responded to downregulation of CYC-B gene expression. In summary, we provide direct evidences that CYC-B gene is involved in carotenoid accumulation and coloration in the loquat.
Global Screening of Genomic and Transcriptomic Factors Associated with Phenotype Differences between Multidrug-Resistant and -Susceptible Candida haemulonii Strains

A comprehensive, multi-omic survey was performed to disclose the genetic backgrounds and differences between multidrug-resistant and -susceptible C. haemulonii strains. Genes were identified with mutations or significant expression differences in multidrug-resistant compared to multidrug-susceptible strains, which were mainly involved in multidrug resistance, stress fitness, and morphology. The Cdr1-encoding gene, C. haemulonii 2486 (CH_2486), was expressed at a significantly increased level in multidrug-resistant strains. Functional inhibition experiments further implicated potential roles of CH_2486 in drug resistance. A gene spontaneously mutated in resistant strains, CH_4347, was experimentally validated to influence the morphology of spores, possibly by controlling cell wall integrity. ABSTRACT Candida haemulonii, a close relative of Candida auris, is an emerging pathogen which frequently shows multidrug resistance especially to triazoles, the most used antifungal drugs. The mechanisms of drug resistance in C. haemulonii, however, are largely unknown. Here, we sequenced and annotated the genomes of two reference strains from the C. haemulonii complex, compared the phenotypes, genomes, and transcriptomes of a triazole-susceptible and two triazole-resistant C. haemulonii strains, and identified triazole susceptibility, morphology, fitness, and the major genetic and gene expression differences between the strains. A multidrug efflux gene, CDR1, was recurrently found to be upregulated for expression in triazole-resistant strains. Blocking the activity of Cdr1 increased the susceptibility to triazoles strikingly. Comparative transcriptome analysis also demonstrated impaired cell wall integrity, filamentous growth, and iron homeostasis in triazole-resistant strains. Finally, we also identified a zinc-binding MHR family transcription regulator gene that mutated in triazole-resistant strains spontaneously, contributing to the changes of morphology and, possibly, cell wall integrity between the strains. The study provided important clues for future studies exploring the mechanisms of multidrug resistance and related phenotypic differences of C. haemulonii strains. IMPORTANCE A comprehensive, multi-omic survey was performed to disclose the genetic backgrounds and differences between multidrug-resistant and -susceptible C. haemulonii strains. Genes were identified with mutations or significant expression differences in multidrug-resistant compared to multidrug-susceptible strains, which were mainly involved in multidrug resistance, stress fitness, and morphology. The Cdr1-encoding gene, C. haemulonii 2486 (CH_2486), was expressed at a significantly increased level in multidrug-resistant strains. Functional inhibition experiments further implicated potential roles of CH_2486 in drug resistance. A gene spontaneously mutated in resistant strains, CH_4347, was experimentally validated to influence the morphology of spores, possibly by controlling cell wall integrity.
Acupuncture Reduces Apoptosis of Granulosa Cells in Rats with Premature Ovarian Failure Via Restoring the PI3K/Akt Signaling Pathway

Acupuncture is widely recognized as an effective therapy for premature ovarian failure (POF) in clinical, but information about its potential mechanisms is rarely explored. To investigate the mechanism, fifty SD female rats were randomly divided into normal group, POF group, POF+estradiol-valerate group (abbreviated as estradiol group), and POF+acupuncture group (abbreviated as acupuncture group). The estrous cycle of the rats was tracked by vaginal smears. Their ovaries morphology was observed by hematoxylin-eosin staining. The apoptotic level of granulosa cells was detected by in situ TUNEL fluorescence staining assay. Serum follicle-stimulating hormone (FSH) and estrogen (E2) levels were measured by enzyme-linked-immunosorbent-assay (ELISA). Protein and gene expression of PI3K, Akt, bcl-2, and bax were detected by Western blotting and qPCR. In the acupuncture and estradiol groups, compared with the POF group as controls, the apoptosis number of granulosa cells was significantly decreased (p < 0.05). FSH levels were decreased, while E2 levels were increased (p > 0.05). The gene and protein expression levels of PI3K, Akt, and bcl-2 were increased, while the expression levels of bax were decreased (p < 0.05), and the protein expression level of p-Akt increased. There was no significant difference between the acupuncture group and the estradiol group (p > 0.05). Acupuncture was able to regulate hormone levels in POF rats, up-regulate PI3K/Akt signaling pathway, and reduce the apoptosis of granulosa cells. This may be one of the mechanisms of acupuncture treating premature ovarian failure.
The Role of Resistance Training Dosing on Pain and Physical Function in Individuals With Knee Osteoarthritis: A Systematic Review

Context: Dosing parameters are needed to ensure the best practice guidelines for knee osteoarthritis. Objective: To determine whether resistance training affects pain and physical function in individuals with knee osteoarthritis, and whether a dose-response relationship exists. Second, we will investigate whether the effects are influenced by Kellgren-Lawrence grade or location of osteoarthritis. Data Sources: A search for randomized controlled trials was conducted in MEDLINE, Embase, and CINAHL, from their inception dates, between November 1, 2018, and January 15, 2019. Keywords included knee osteoarthritis, knee joint, resistance training, strength training, and weight lifting. Study Selection: Inclusion criteria were randomized controlled trials reporting changes in pain and physical function on humans with knee osteoarthritis comparing resistance training interventions with no intervention. Two reviewers screened 471 abstracts; 12 of the 13 studies assessed were included. Study Design: Systematic review. Level of Evidence: Level 2. Data Extraction: Mean baseline and follow-up Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and standard deviations were extracted to calculate the standard mean difference. Articles were assessed for methodological quality using the CONSORT (Consolidated Standards of Reporting Trials) 2010 scale and Cochrane Collaboration tool for assessing risk of bias. Results: The 12 included studies had high methodological quality. Of these, 11 studies revealed that resistance training improved pain and/or physical function. The most common regimen was a 30- to 60-minute session of 2 to 3 sets of 8 to 12 repetitions with an initial resistance of 50% to 60% of maximum resistance that progressed over 3 sessions per week for 24 weeks. Seven studies reported Kellgren-Lawrence grade, and 4 studies included osteoarthritis location. Conclusion: Resistance training improves pain and physical function in knee osteoarthritis. Large effect sizes were associated with 24 total sessions and 8- to 12-week duration. No optimal number of repetitions, maximum strength, or frequency of sets or repetitions was found. No trends were identified between outcomes and location or Kellgren-Lawrence grade of osteoarthritis.
Cold Atmospheric Plasma Restores Paclitaxel Sensitivity to Paclitaxel-Resistant Breast Cancer Cells by Reversing Expression of Resistance-Related Genes

Paclitaxel (Tx) is a widely used therapeutic chemical for breast cancer treatment; however, cancer recurrence remains an obstacle for improved prognosis of cancer patients. In this study, cold atmospheric plasma (CAP) was tested for its potential to overcome the drug resistance. After developing Tx-resistant MCF-7 (MCF-7/TxR) breast cancer cells, CAP was applied to the cells, and its effect on the recovery of drug sensitivity was assessed in both cellular and molecular aspects. Sensitivity to Tx in the MCF-7/TxR cells was restored up to 73% by CAP. A comparison of genome-wide expression profiles between the TxR cells and the CAP-treated cells identified 49 genes that commonly appeared with significant changes. Notably, 20 genes, such as KIF13B, GOLM1, and TLE4, showed opposite expression profiles. The protein expression levels of selected genes, DAGLA and CEACAM1, were recovered to those of their parental cells by CAP. Taken together, CAP inhibited the growth of MCF-7/TxR cancer cells and recovered Tx sensitivity by resetting the expression of multiple drug resistance–related genes. These findings may contribute to extending the application of CAP to the treatment of TxR cancer.
Improving the Quantification of DNA Sequences Using Evolutionary Information Based on Deep Learning

It is known that over 98% of the human genome is non-coding, and 93% of disease associated variants are located in these regions. Therefore, understanding the function of these regions is important. However, this task is challenging as most of these regions are not well understood in terms of their functions. In this paper, we introduce a novel computational model based on deep neural networks, called DQDNN, for quantifying the function of non-coding DNA regions. This model combines convolution layers for capturing regularity motifs at multiple scales and recurrent layers for capturing long term dependencies between the captured motifs. In addition, we show that integrating evolutionary information with raw genomic sequences improves the performance of the predictor significantly. The proposed model outperforms the state-of-the-art ones using raw genomics sequences only and also by integrating evolutionary information with raw genomics sequences. More specifically, the proposed model improves 96.9% and 98% of the targets in terms of area under the receiver operating characteristic curve and the precision-recall curve, respectively. In addition, the proposed model improved the prioritization of functional variants of expression quantitative trait loci (eQTLs) compared with the state-of-the-art models.
Effect of a Computer-Based Decision Support Intervention on Autism Spectrum Disorder Screening in Pediatric Primary Care Clinics

Key Points Question Can computer automation coupled with decision support increase timely screening for autism spectrum disorders in primary care practice? Findings This cluster randomized clinical trial found that computer-based screening and decision support embedded into the routine workflow in primary care increased rates of screening from 0% to 100%, but physicians responded to approximately half of positive screening results. Meaning Automating the screening process can ensure that screening takes place, but follow-through of the results is vulnerable to human error.
Correlation of mRNA delivery timing and protein expression in lipid-based transfection

Non-viral gene delivery is constrained by the dwell time that most synthetic nucleic acid nanocarriers spend inside endosomal compartments. In order to overcome this endosomal-release bottleneck, methods are required that measure nanocarrier uptake kinetics and transfection efficiency simultaneously. Here, we employ live-cell imaging on single-cell arrays (LISCA) to study the delivery-time distribution of lipid-based mRNA complexes under varied serum conditions. By fitting a translation-maturation model to hundreds of individual eGFP reporter fluorescence time courses, the protein expression onset times and the expression rates after transfection are determined. Using this approach, we find that delivery timing and protein expression rates are not intrinsically correlated at the single-cell level, even though population-averaged values of both parameters conjointly change as a function of increasing external serum protein fraction. Lipofectamine mediated delivery showed decreased transfection efficiency and longer delivery times with increasing serum protein concentration. This is in contrast to ionizable lipid nanoparticles (LNPs) mediated transfer, which showed increased efficiency and faster uptake in the presence of serum. In conclusion, the interdependences of single-cell expression rates and onset timing provide additional clues on uptake and release mechanisms, which are useful for improving nucleic acid delivery.
Ecotoxicology and Environmental Safety Microplastics and seafood: lower trophic organisms at highest risk of contamination

Microplastic debris is a prevalent global pollutant that poses a risk to marine organisms and ecological processes. It is also suspected to pose a risk to marine food security; however, these risks are currently poorly understood. In this review, we seek to understand the current knowledge pertaining to the contamination of commercially important ﬁ shed and farmed marine organisms with microplastics, with the aim of answering the question “ Does microplastic pollution pose a risk to marine food security? “ . A semi-systematic review of studies investigating the number of microplastics found in commercially important organisms of di ﬀ erent trophic levels suggests that microplastics do not biomagnify, and that organisms at lower trophic levels are more likely to contaminated by microplastic pollution than apex predators. We address the factors that in ﬂ uence microplastic consumption and retention by organisms. This research has implications for food safety and highlights the risks of microplastics to ﬁ sheries and aquaculture, and identi ﬁ es current knowledge gaps within this research ﬁ eld.
Time intervals between lengthening of growing rods can influence effectiveness in the treatment of early onset scoliosis

Objective: The aim of the current study was to investigate the influence of different time intervals between lengthening of growing rods on effectiveness levels in the treatment of early onset scoliosis. Method: A retrospective study of patients undergoing GR treatment, from July 2002 to February 2016, was conducted. This study defined lengthening at a 12-month interval as a research event in group A and two continuous lengthenings at 6-month intervals as a research event in group B. Therapeutic outcomes at the end of the events were compared between the two groups. The impact of different factors on therapeutic outcomes was analyzed using multiple linear regression analysis. Present findings were confirmed by independent sample t-tests and covariance. Result: Multiple linear regression analysis showed that different time intervals between lengthenings were the only factors of improvement of T1-S1 length and sitting heights. In addition, both preoperative Cobb angles (starting point) and gender could affect changes in the Cobb angle and standing heights (P=0). Further analysis by ANCOVA and independent sample t-tests showed that the cobb angle change in group A was 12.04° ± 1.08°. T1-S1 increased by 1.05 ± 0.72 cm and the sitting height increased by 2.52 ± 1.40 cm. Standing height increased by 5.64 ± 1.84 cm. In group B, the change in the cobb angle was 23.49° ± 1.16°. T1-S1 increased by 1.97 ± 0.88 cm and the sitting height increased by 3.84 ± 1.82 cm. Standing height increased by 7.72 ± 2.99 cm. A total of 10 implant-related complications occurred in group A. No implant-related complications occurred in group B. Differences between group A and group B were statistically significant (P<0.05). Conclusion: There was greater growth and correction, as well as fewer complications, in those lengthened at 6 months, compared with those lengthened at 12 months.
Using Manufacturing Simulations to Evaluate Metacognitive Awareness in Industrial Engineering Students

Metacognition is the process of “thinking about thinking” such that individuals learn methods to understand the way that they learn, what they are lacking in their current learning strategies, and how to improve. Metacognition is an important dimension of problem solving because it allows problem solvers to analyze problems and find viable solutions. In design and manufacturing, problem solving focuses on optimizing the product design and improving the production process. In this paper, we discuss the development of physical simulation games to evaluate metacognitive awareness in industrial engineering students. In order to develop metacognitive awareness, students participate in group manufacturing simulations and each group evaluate the work of other groups. Metacognitive awareness inventory (MAI) is used to evaluate the metacognitive awareness of the students before and after their participation in the simulation activities. MAI is an instrument designed to assess general self-regulated learning skills. The instrument has 52 items that are classified by type of cognitive knowledge: declarative (DK), procedural (PK), and conditional (CK); or by specific metacognitive process: planning (P), information management strategies (IMS), monitoring (M), debugging strategies (DS), and evaluation (E). Results show that the students improved their metacognitive awareness for all the MAI categories. However, only the improvement in the last three categories (i.e., M, DS, and E) was statistically significant.
Designing Technology to Support Empathy for Rural Community

In isolated, rural areas, people are necessarily independent and it can be difficult for them to seek help. One of the ways to improve this is to find a remotely accessible solution. Information and communication technology (ICT) can be used to eliminate distance as a barrier to social interaction, and in turn can create new optimism for rural areas when it is a device to improve interaction. The important benefit of receiving emotional support and information from others is that it encourages and increases hope. This research suggests that when collaborating virtually, the farming community can receive effective advice from experts to facilitate their decision making and at the same time to support their psychosocial health. The user experience of the emotional expression in the discussion among community members will be highlighted. We posit that it is important that empathy and hope are included in interaction between participants, especially when ICT is used to deal with complex conversations (e.g. climate change, agricultural