Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of the Morphological Plasticity Induced by Phytohormones and the Environment in Plants

Plants adapt to environmental changes by regulating their development and growth. As an important interface between plants and their environment, leaf morphogenesis varies between species, populations, or even shows plasticity within individuals. Leaf growth is dependent on many environmental factors, such as light, temperature, and submergence. Phytohormones play key functions in leaf development and can act as molecular regulatory elements in response to environmental signals. In this review, we discuss the current knowledge on the effects of different environmental factors and phytohormone pathways on morphological plasticity and intend to summarize the advances in leaf development. In addition, we detail the molecular mechanisms of heterophylly, the representative of leaf plasticity, providing novel insights into phytohormones and the environmental adaptation in plants.
The Nutritional Status of Individuals Adopted Internationally as Children: A Systematic Review

Since 1955, international adoption has been a way of finding homes for children who have been orphaned or abandoned. We aimed to describe the nutritional status of individuals adopted internationally and their long-term nutritional and health outcomes. We searched four databases for articles published from January 1995 to June 2020, which included information on anthropometric or micronutrient status of children adopted internationally (CAI). Mean Z-scores on arrival to adoptive country ranged from −2.04 to −0.31 for weight for age; −0.94 to 0.39 for weight for height; −0.7 to 0 for body mass index; −1.89 to −0.03 for height for age; −1.43 to 0.80 for head circumference for age. Older children, those adopted from institutionalized care or with underlying disability, were more likely to be malnourished. Though long-term data was scarce, mean Z-scores post-adoption ranged from −0.59 to 0.53 for weight for age; −0.31 to 1.04 for weight for height; 0.39 to 1.04 for body mass index; −1.09 to 0.58 for height for age; −0.06 to 1.23 for head circumference for age. We conclude that though CAI are at high risk of malnutrition at baseline, marked catch-up growth is possible, including for those older than two years of age on arrival. This has implications not only for CAI but for the wider population of malnourished children worldwide. Research on how to optimize catch-up growth is a priority.
SARS-CoV-2/human interactome reveals ACE2 locus crosstalk with the immune regulatory network in the host.

Severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), remains to be a threat across the globe. SARS-CoV-2 entry to the host-mediated by binding of viral spike protein to the Human angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is an essential member of the Renin-Angiotensin system (RAS) involved in maintaining blood pressure and vascular remodelling. Although ACE2 receptor is the entry point to the host, recent studies show activation of ACE2 to modulate the host to develop a suitable environment for its replication. However, the ACE2 activating the immune signals on SARS-CoV-2 attachment is still under investigation. We have used a systems biological approach to construct the host regulatory network upon SARS-CoV-2 attachment to the ACE2 receptor. Since lungs are the primary infection site, we integrate human lung gene expression profile along with the host regulatory network to demonstrate the altered host signalling mechanism on viral infection. Further, the network was functionally enriched to determine immune modulation in the network. We also used the proteomic database to assess the occurrence of similar signalling events in other human tissue that exhibits lineage of infection across different organs. The constructed network contains 133 host proteins with 298 interactions that directly or indirectly connect to the ACE2 receptor. Among 133 proteins, 29 found to be differentially regulated in the host lungs on SARS-CoV-2 infection. Altered proteins connect multiple proteins in a network that modulates kinase, carboxypeptidase and cytokine activity, leading to change in the host immune system, cell cycle, and signal transduction mechanism. Further investigation showed the presence of similar signalling events in the kidney, placenta, pancreas, testis, stomach, small intestine and adrenal gland suggesting the possible the mechanistic lineage of viral infection in other tissue. Overall, our results will help advance our understanding of the immune molecular regulatory network influenced by the ACE2 mediated interaction in other body tissues, which could help in finding the secondary health complications associated with SARS-CoV-2 infection.
Genome‐wide chromatin occupancy of BRDT and gene expression analysis suggest transcriptional partners and specific epigenetic landscapes that regulate gene expression during spermatogenesis

BRDT, a member of the BET family of double bromodomain‐containing proteins, is essential for spermatogenesis in the mouse and has been postulated to be a key regulator of transcription in meiotic and post‐meiotic cells. To understand the function of BRDT in these processes, we first characterized the genome‐wide distribution of the BRDT binding sites, in particular within gene units, by ChIP‐Seq analysis of enriched fractions of pachytene spermatocytes and round spermatids. In both cell types, BRDT binding sites were mainly located in promoters, first exons, and introns of genes. BRDT binding sites in promoters overlapped with several histone modifications and histone variants associated with active transcription, and were enriched for consensus sequences for specific transcription factors, including MYB, RFX, ETS, and ELF1 in pachytene spermatocytes, and JunD, c‐Jun, CRE, and RFX in round spermatids. Subsequent integration of the ChIP‐seq data with available transcriptome data revealed that stage‐specific gene expression programs are associated with BRDT binding to their gene promoters, with most of the BDRT‐bound genes being upregulated. Gene Ontology analysis further identified unique sets of genes enriched in diverse biological processes essential for meiosis and spermiogenesis between the two cell types, suggesting distinct developmentally stage‐specific functions for BRDT. Taken together, our data suggest that BRDT cooperates with different transcription factors at distinctive chromatin regions within gene units to regulate diverse downstream target genes that function in male meiosis and spermiogenesis.
Circular RNAs: Potential Applications as Therapeutic Targets and Biomarkers in Breast Cancer

Circular RNAs (circRNAs) are a class of non-coding RNAs that form a covalently closed loop. A number of functions and mechanisms of action for circRNAs have been reported, including as miRNA sponge, exerting transcriptional and translational regulation, interacting with proteins, and coding for peptides. CircRNA dysregulation has also been implicated in many cancers, such as breast cancer. Their relatively high stability and presence in bodily fluids makes cancer-associated circRNAs promising candidates as a new biomarker. In this review, we summarize the research undertaken on circRNAs associated with breast cancer, discuss circRNAs as biomarkers, and present circRNA-based therapeutic approaches.
Pyrrolizidine Alkaloids Disturb Bile Acid Homeostasis in the Human Hepatoma Cell Line HepaRG

1,2-unsaturated pyrrolizidine alkaloids (PAs) belong to a group of secondary plant metabolites. Exposure to PA-contaminated feed and food may cause severe hepatotoxicity. A pathway possibly involved in PA toxicity is the disturbance of bile acid homeostasis. Therefore, in this study, the influence of four structurally different PAs on bile acid homeostasis was investigated after single (24 h) and repeated (14 days) exposure using the human hepatoma cell line HepaRG. PAs induce a downregulation of gene expression of various hepatobiliary transporters, enzymes involved in bile acid synthesis, and conjugation, as well as several transcription regulators in HepaRG cells. This repression may lead to a progressive impairment of bile acid homeostasis, having the potential to accumulate toxic bile acids. However, a significant intracellular and extracellular decrease in bile acids was determined, pointing to an overall inhibition of bile acid synthesis and transport. In summary, our data clearly show that PAs structure-dependently impair bile acid homeostasis and secretion by inhibiting the expression of relevant genes involved in bile acid homeostasis. Furthermore, important biliary efflux mechanisms seem to be disturbed due to PA exposure. These mole-cular mechanisms may play an important role in the development of severe liver damage in PA-intoxicated humans.
Characterising polypharmacy in the very old: Findings from the Newcastle 85+ Study

Background Polypharmacy is potentially harmful and under-researched amongst the fastest growing subpopulation, the very old (aged ≥85). We aimed to characterise polypharmacy using data from the Newcastle 85+ Study—a prospective cohort of people born in 1921 who turned 85 in 2006 (n = 845). Methods The prevalence of polypharmacy at baseline (mean age 85.5) was examined using cut-points of 0, 1, 2–4, 5–9 and ≥10 medicines—so-called ‘no polypharmacy’, ‘monotherapy’, ‘minor polypharmacy’, ‘polypharmacy’ and ‘hyperpolypharmacy. ’ Cross-tabulations and upset plots identified the most frequently prescribed medicines and medication combinations within these categories. Mixed-effects models assessed whether gender and socioeconomic position were associated with prescribing changes over time (mean age 85.5–90.5). Participant characteristics were examined through descriptive statistics. Results Complex multimorbidity (44.4%, 344/775) was widespread but hyperpolypharmacy was not (16.0%, 135/845). The median medication count was six (interquartile range 4–8). Preventative medicines were common to all polypharmacy categories, and prescribing regimens were diverse. Nitrates and oral anticoagulants were more frequently prescribed for men, whereas bisphosphonates, non-opioid analgesics and antidepressants were more common in women. Cardiovascular medicines, including loop diuretics, tended to be more frequently prescribed for socioeconomically disadvantaged people (<25th centile Index of Multiple Deprivation (IMD)), despite no difference in the prevalence of cardiovascular disease (p = 0.56) and diabetes (p = 0.92) by IMD. Conclusion Considering their complex medical conditions, prescribing is relatively conservative amongst 85-year-olds living in North East England. Prescribing shows significant gender and selected socioeconomic differences. More support for managing preventative medicines, of uncertain benefit, might be helpful in this population.
Bacterial fitness landscapes stratify based on proteome allocation associated with discrete aero-types

The fitness landscape is a concept commonly used to describe evolution towards optimal phenotypes. It can be reduced to mechanistic detail using genome-scale models (GEMs) from systems biology. We use recently developed GEMs of Metabolism and protein Expression (ME-models) to study the distribution of Escherichia coli phenotypes on the rate-yield plane. We found that the measured phenotypes distribute non-uniformly to form a highly stratified fitness landscape. Systems analysis of the ME-model simulations suggest that this stratification results from discrete ATP generation strategies. Accordingly, we define “aero-types”, a phenotypic trait that characterizes how a balanced proteome can achieve a given growth rate by modulating 1) the relative utilization of oxidative phosphorylation, glycolysis, and fermentation pathways; and 2) the differential employment of electron-transport-chain enzymes. This global, quantitative, and mechanistic systems biology interpretation of fitness landscape formed upon proteome allocation offers a fundamental understanding of bacterial physiology and evolution dynamics.
Machine Learning Techniques for Hypoglycemia Prediction: Trends and Challenges

(1) Background: the use of machine learning techniques for the purpose of anticipating hypoglycemia has increased considerably in the past few years. Hypoglycemia is the drop in blood glucose below critical levels in diabetic patients. This may cause loss of cognitive ability, seizures, and in extreme cases, death. In almost half of all the severe cases, hypoglycemia arrives unannounced and is essentially asymptomatic. The inability of a diabetic patient to anticipate and intervene the occurrence of a hypoglycemic event often results in crisis. Hence, the prediction of hypoglycemia is a vital step in improving the life quality of a diabetic patient. The objective of this paper is to review work performed in the domain of hypoglycemia prediction by using machine learning and also to explore the latest trends and challenges that the researchers face in this area; (2) Methods: literature obtained from PubMed and Google Scholar was reviewed. Manuscripts from the last five years were searched for this purpose. A total of 903 papers were initially selected of which 57 papers were eventually shortlisted for detailed review; (3) Results: a thorough dissection of the shortlisted manuscripts provided an interesting split between the works based on two categories: hypoglycemia prediction and hypoglycemia detection. The entire review was carried out keeping this categorical distinction in perspective while providing a thorough overview of the machine learning approaches used to anticipate hypoglycemia, the type of training data, and the prediction horizon.
Deep Temporal Convolution Network for Time Series Classification

A neural network that matches with a complex data function is likely to boost the classification performance as it is able to learn the useful aspect of the highly varying data. In this work, the temporal context of the time series data is chosen as the useful aspect of the data that is passed through the network for learning. By exploiting the compositional locality of the time series data at each level of the network, shift-invariant features can be extracted layer by layer at different time scales. The temporal context is made available to the deeper layers of the network by a set of data processing operations based on the concatenation operation. A matching learning algorithm for the revised network is described in this paper. It uses gradient routing in the backpropagation path. The framework as proposed in this work attains better generalization without overfitting the network to the data, as the weights can be pretrained appropriately. It can be used end-to-end with multivariate time series data in their raw form, without the need for manual feature crafting or data transformation. Data experiments with electroencephalogram signals and human activity signals show that with the right amount of concatenation in the deeper layers of the proposed network, it can improve the performance in signal classification.
A 4-tier Protocolized Radiological Classification System for Leaks Following Sleeve Gastrectomy

Supplemental Digital Content is available in the text Objectives: To develop and validate a classification of sleeve gastrectomy leaks able to reliably predict outcomes, from protocolized computed tomography (CT) findings and readily available variables. Summary of Background Data: Leaks post sleeve gastrectomy remain morbid and resource-consuming. Incidence, treatments, and outcomes are variable, representing heterogeneity of the problem. A predictive tool available at presentation would aid management and predict outcomes. Methods: From a prospective database (2009–2018) we reviewed patients with staple line leaks. A Delphi process was undertaken on candidate variables (80–20). Correlations were performed to stratify 4 groupings based on outcomes (salvage resection, length of stay, and complications) and predictor variables. Training and validation cohorts were established by block randomization. Results: A 4-tiered classification was developed based on CT appearance and duration postsurgery. Interobserver agreement was high (κ = 0.85, P < 0.001). There were 59 patients, (training: 30, validation: 29). Age 42.5 ± 10.8 versus 38.9 ± 10.0 years (P = 0.187); female 65.5% versus 80.0% (P = 0.211), weight 127.4 ± 31.3 versus 141.0 ± 47.9 kg, (P = 0.203). In the training group, there was a trend toward longer hospital stays as grading increased (I = 10.5 d; II = 24 d; III = 66.5 d; IV = 72 d; P = 0.005). Risk of salvage resection increased (risk ratio grade 4 = 9; P = 0.043) as did complication severity (P = 0.027). Findings were reproduced in the validation group: risk of salvage resection (P = 0.007), hospital stay (P = 0.001), complications (P = 0.016). Conclusion: We have developed and validated a classification system, based on protocolized CT imaging that predicts a step-wise increased risk of salvage resection, complication severity, and increased hospital stay. The system should aid patient management and facilitate comparisons of outcomes and efficacy of interventions.
MicroRNAs for Virus Pathogenicity and Host Responses, Identified in SARS-CoV-2 Genomes, May Play Roles in Viral-Host Co-Evolution in Putative Zoonotic Host Species

Our recent study identified seven key microRNAs (miR-8066, 5197, 3611, 3934-3p, 1307-3p, 3691-3p, 1468-5p) similar between SARS-CoV-2 and the human genome, pointing at miR-related mechanisms in viral entry and the regulatory effects on host immunity. To identify the putative roles of these miRs in zoonosis, we assessed their conservation, compared with humans, in some key wild and domestic animal carriers of zoonotic viruses, including bat, pangolin, pig, cow, rat, and chicken. Out of the seven miRs under study, miR-3611 was the most strongly conserved across all species; miR-5197 was the most conserved in pangolin, pig, cow, bat, and rat; miR-1307 was most strongly conserved in pangolin, pig, cow, bat, and human; miR-3691-3p in pangolin, cow, and human; miR-3934-3p in pig and cow, followed by pangolin and bat; miR-1468 was most conserved in pangolin, pig, and bat; while miR-8066 was most conserved in pangolin and pig. In humans, miR-3611 and miR-1307 were most conserved, while miR-8066, miR-5197, miR-3334-3p and miR-1468 were least conserved, compared with pangolin, pig, cow, and bat. Furthermore, we identified that changes in the miR-5197 nucleotides between pangolin and human can generate three new miRs, with differing tissue distribution in the brain, lung, intestines, lymph nodes, and muscle, and with different downstream regulatory effects on KEGG pathways. This may be of considerable importance as miR-5197 is localized in the spike protein transcript area of the SARS-CoV-2 genome. Our findings may indicate roles for these miRs in viral–host co-evolution in zoonotic hosts, particularly highlighting pangolin, bat, cow, and pig as putative zoonotic carriers, while highlighting the miRs’ roles in KEGG pathways linked to viral pathogenicity and host responses in humans. This in silico study paves the way for investigations into the roles of miRs in zoonotic disease.
Refinement of a Live Attenuated Salmonella enterica Serovar Newport Vaccine with Improved Safety

Non-typhoidal Salmonella (NTS) is a major cause of gastroenteritis and is responsible for approximately 93 million cases annually. In healthy individuals, gastroenteritis caused by NTS is usually self-limiting, however, NTS can cause severe invasive disease in immunocompromised patients. Very little research has been directed towards development of vaccines against Salmonella serogroups O:6,7 or O:8. We have constructed a live attenuated serogroup O:8 vaccine, CVD 1979, by deleting guaBA, htrA, and aroA from the genome of S. Newport. We have shown that the candidate vaccine is well tolerated in mice and elicits serum immunoglobulin G (IgG) antibodies against core O-polysaccharide (COPS) when administered orally. Immunized mice were challenged intraperitoneally with wild-type S. Newport and bacterial burden in the liver and spleen was found to be significantly reduced in the livers of immunized mice compared to control mice. We also observed moderate vaccine efficacy (45%) against lethal challenge with the serogroup O:8 serovar, S. Muenchen, but low vaccine efficacy (28%) following lethal challenge with a serogroup O:6,7 serovar, S. Virchow. In vitro, we have shown that antibodies generated by CVD 1979 only recognize lipopolysaccharide (LPS) from serogroup O:8 but not serogroup O:6,7 serovars, and that they mediate opsonophagocytic antibody (OPA) activity against serogroup O:8 but not serogroup O:6,7 serovars. We also showed that OPA activity can be blocked by pre-incubating the antisera with serogroup O:8 lipopolysaccharide. Taken together, our data demonstrate that we have constructed a well-tolerated, effective live attenuated S. Newport vaccine which elicits functional antibodies against serogroup O:8 but not O:6,7 serovars.
Selective photooxidation of light alkanes to oxygenates using supported molybdenum oxide catalysts

Photo-assisted catalytic partial oxidation of methane, ethane and propane has been performed in the presence of supported molybdenum oxide catalysts at around 500 K by the use of a fluidized bed flow-type reactor under UV irradiation. Temperatures as high as 500 K were indispensable for the selective formation of methanal from methane (ca. 19 µmol h–1), corresponding to 5.5% of the photons irradiated into the catalyst bed ( <300 nm). The yields were greatly affected by the loding levels of molybdenum species, the preparation methods of the catalysts and the light flux into the catalyst bed. Photooxidation of ethane and propane also selectively gave the corresponding aldehydes and ketones in high yields (ca. 80 µmol h–1) at elevated temperature. The reaction seemed to proceed via charge-transfer complexes formed by photo-activation of terminal coordinatively unsaturated MO groups in multilayers of molybdenum species.